Identification of two novel mutations in three children with congenital factor VII deficiency

Liang, Kairong; Nikuze, Lauriane; Zhang, Fuyong; Lu, Zhengjing; Wei, Manlv; Wei, Hongying

doi:10.1097/mbc.0000000000001022

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…Bioinformatics analyses found these variations pathogenic (49). In another study, Liang et al detected two novel variations in three patients with FVII deficiency; the molecular model analysis of the two novel mutations (Cys115Arg and Pro324Leu) indicated impairment of the proper folding of the EGF1 domain and impairment of the F7 coagulant activity (50). Cys164Tyr, another novel mutation, was found in a patient with mild clinical manifestations despite deficient FVII activity (51).…”

Section: F7 Gene Variationsmentioning

confidence: 99%

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

Mashayekhi

Ghasemi

2022

Trends in Med Sci

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: Coagulation factor VII (FVII) is a vitamin K-dependent serine protease that plays a pivotal role in normal hemostasis. Mature FVII is a glycoprotein comprised γ-carboxyglutamic acid-rich (Gla) domain, two epidermal growth factor (EGF)-like domains, an activation domain, and a serine protease domain. FVII requires proteolytic activation followed by tissue factor (TF) binding for maximal activity. The F7 gene (14.8 kb) is located on 13q34, composed of nine exons and eight introns. The congenital FVII deficiency is a rare coagulopathy with an autosomal recessive pattern of inheritance that occurs due to mutation in the F7 gene. A considerable number of mutations of different types have been identified throughout this gene affecting the expression, structure, and post-translational alterations of the protein. FVII deficiency is the most frequently recessively inherited bleeding disorder. Subjects with FVII deficiency show a wide range of symptoms, including cutaneous hemorrhage, mucosal hemorrhage, gastrointestinal bleeding, joint bleeding, and central nervous system (CNS) hemorrhage. Unlike other coagulation factor deficiencies, serum levels of FVII do not demonstrate the severity of the disease, and there is no direct correlation between serum levels and clinical complications. Replacement therapy is the treatment of choice for FVII deficiency. Various therapeutic products such as prothrombin complex concentrate, plasma-derived FVII concentrate, fresh frozen plasma, and activated recombinant FVII are available to treat FVII deficient individuals. This review aims to provide information on molecular, biochemical, and clinical aspects of coagulation FVII, its role in hemostasis, and the consequences of its deficiency.

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Section: F7 Gene Variationsmentioning

confidence: 99%

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

Mashayekhi

Ghasemi

2022

Trends in Med Sci

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“…A homozygous mutation of IVS7+1G>T in the FVII gene splice site led to severe gastrointestinal tract and intracranial hemorrhage 8 . Cys115Arg and Pro324Leu, situated on the F7 gene, were responsible for the impairment of the proper folding of the EGF 1 domain, which led to congenital deficiency of FVII 9 . Phe84Ser and p.Gly156Cys affected the Gla and EGF domains of FVII, respectively, causing hereditary coagulation factor VII deficiency 10 …”

Section: Introductionmentioning

confidence: 99%

Hereditary coagulation factor VII deficiency caused by novel compound heterozygous mutations in a Chinese pedigree: A case report

Cai

et al. 2022

Clinical Laboratory Analysis

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Background Congenital coagulation factor VII (FVII) deficiency is a rare, autosomal‐recessive haemorrhagic disorder with an estimated incidence of 1:500,000. This disorder is caused by mutations in the F7 gene. Case description Here, we report a pedigree of congenital FVII deficiency. The proband was a 30‐year‐old female with severely low FVII activity and a history of menorrhagia and epistaxis since her childhood who was subsequently diagnosed with congenital compound heterozygous FVII deficiency. A genetic study revealed a novel combination of compound heterozygous mutations (c.64G 〉 A, p.Gly22Ser and c.1027G 〉 A, p.Gly343Ser). Her father and older son had the c.64G 〉 A, p.Gly22Ser (heterozygous) mutation. Her mother and younger son had the c.1027G 〉 A, p.Gly343Ser (heterozygous) mutation. The predicted results of PolyPhen‐2 and MutationTaster indicated that these mutations were probably damaging and disease‐causing, respectively. Conclusion In this study, we identified a novel combination of genetic mutations that could expand the mutant library and help in elucidating the pathogenesis of hereditary human coagulation FVII deficiency. A novel combination of compound heterozygous mutations was reported for the first time in Chinese individuals.

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Identification of two novel mutations in three children with congenital factor VII deficiency

Cited by 2 publications

References 16 publications

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

Hereditary coagulation factor VII deficiency caused by novel compound heterozygous mutations in a Chinese pedigree: A case report

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